Publications by authors named "Noel R Park"
Many genes that drive normal cellular development also contribute to oncogenesis. Medulloblastoma (MB) tumors likely arise from neuronal progenitors in the cerebellum, and we hypothesized that the heterogeneity observed in MBs with sonic hedgehog (SHH) activation could be due to differences in developmental pathways. To investigate this question, here we perform single-nucleus RNA sequencing on highly differentiated SHH MBs with extensively nodular histology and observed malignant cells resembling each stage of canonical granule neuron development.
View Article and Find Full Text PDFDetection of small molecule metabolites (SMM), particularly those involved in energy metabolism using MALDI-mass spectrometry imaging (MSI), is challenging due to factors including ion suppression from other analytes present (e.g., proteins and lipids).
View Article and Find Full Text PDFTissues derive ATP from two pathways-glycolysis and the tricarboxylic acid (TCA) cycle coupled to the electron transport chain. Most energy in mammals is produced via TCA metabolism. In tumours, however, the absolute rates of these pathways remain unclear.
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- Tumor-infiltrating immune cells and cancer cells compete for nutrients in the tumor microenvironment, leading to metabolic reprogramming that affects their functions.
- The study introduced a new method using implantable microdevices to analyze how different metabolites impact the health and endurance of immune versus tumor cells within the native tumor environment.
- Key findings highlight the importance of metabolites like glutamine and arginine in enhancing immune responses, and suggest that optimizing these metabolic pathways could improve the effectiveness of immunotherapies in cancer treatment.
Autophagy defects are a risk factor for inflammatory bowel diseases (IBDs) through unknown mechanisms. Whole-body conditional deletion of autophagy-related gene (Atg) Atg7 in adult mice (Atg7Δ/Δ) causes tissue damage and death within 3 mo due to neurodegeneration without substantial effect on intestine. In contrast, we report here that whole-body conditional deletion of other essential Atg genes Atg5 or Fip200/Atg17 in adult mice (Atg5Δ/Δ or Fip200Δ/Δ) caused death within 5 d due to rapid autophagy inhibition, elimination of ileum stem cells, and loss of barrier function.
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- Diffuse large B-cell lymphomas (DLBCL) rely on a metabolic process regulated by mitochondrial SIRT3, and its depletion triggers cell death through reduced levels of ATF4.
- The study indicates that ATF4 production is decreased in SIRT3-deficient cells, which affects amino acid metabolism and survival of DLBCL cells.
- By targeting the SIRT3-ATF4 pathway, researchers suggest potential new therapeutic strategies to enhance the effectiveness of SIRT3 inhibitors in treating DLBCL.
Article Synopsis
- The immune function is crucial for cellular repair and survival, but fighting infections can be energy-intensive, particularly affecting metabolically active organs like the liver.
- Mycoplasma gallisepticum (MG) is an immunosuppressive bacterium that severely impacts songbirds, especially house finches, by causing respiratory and eye infections.
- Research showed MG-infected house finches had lower oxidative damage in their liver compared to uninfected birds, suggesting that MG might suppress liver function to help mitigate immune responses.
Article Synopsis
- Animal life-history patterns focus on maximizing reproduction while managing energy demands, particularly between reproductive activities and self-maintenance.
- In a study on lab mice, it was hypothesized that reproductive history affects mitochondrial performance, predicting that primiparous females would outperform nulliparous mice, while multiparous females would show diminished performance and greater oxidative damage.
- Results indicated that multiple reproductive events improve mitochondrial capacity in higher body mass females, while those that invested heavily in reproduction showed compromised mitochondrial function and increased oxidative stress.
Article Synopsis
- Carotenoid coloration in animals, particularly in birds, is an important signal of individual health, but the exact mechanisms connecting coloration to overall condition have yet to be fully understood.
- A study on wild house finches found that the conversion of dietary carotenoids to red pigments is linked to liver mitochondrial performance, as high levels of red carotenoids were found in liver mitochondria during feather molting.
- The enzyme CYP2J19 plays a crucial role in this process, suggesting that the color of feathers not only reflects health but also indicates underlying cellular respiration and mitochondrial function.
An animal's pace of life is mediated by the physiological demands and stressors it experiences (e.g. reproduction) and one likely mechanism that underlies these effects is oxidative stress.
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- Understanding physiological responses often relies on isolated data from single events, which overlooks how an organism's past experiences shape its physiology over time.
- The concept of carry-over effects suggests that prior experiences can significantly influence performance; for example, increased physical activity can enhance mitochondrial function and promote better health.
- In this study, female mice that exercised prior to mating had larger and heavier litters, demonstrating that physical activity positively impacts reproductive success by enhancing biological functions like mitochondrial respiration.